Gene therapy may offer "functional" cure for HIV

Wed Mar 5, 2014 5:00pm EST

Mar 5 (Reuters) - A strategy to genetically modify cells from people infected with HIV could become a way to control the virus that causes AIDS without using antiviral drugs, according to results from an early-stage trial that were published on Wednesday.

Data from the small study of the Sangamo BioSciences therapy, known by the code name SB-728-T, were issued in the New England Journal of Medicine, the first publication of data from a human trial of a technology called "gene editing."

The technique is designed to disrupt a gene, CCR5, used by HIV to infect T-cells, the white blood cells that fight viral infections. A patient's cells are removed and processed to alter the DNA that codes for the CCR5 receptor. The altered cells are multiplied and tested, then infused back into the patient.

The Phase 1 trial, led by the University of Pennsylvania, enrolled 12 HIV patients. The study's main goal was safety, but it also showed that the modified T-cells persisted and the presence of HIV DNA decreased, the researchers said.

"It's very solid, elegant science," said Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. "There is a strong suggestion that cells that are generated are less susceptible to dying."

Sangamo plans to release more trial results this week in Boston at the Conference on Retroviruses and Opportunistic Infections. It will also discuss strategies to improve patient outcomes.

The gene editing technique seeks to mimic the resistance to HIV observed in the small number of people who have inherited CCR5 mutations from both parents. A patient in the trial who carried a naturally occurring mutation in one copy of the CCR5 gene saw the presence of HIV drop to undetectable levels.

"The target we are going after, CCR5, is the most advanced and most promising approach for a functional cure for HIV," said Sangamo Chief Executive Officer Edward Lanphier.

The human immunodeficiency virus, or HIV, surfaced more than 30 years ago and now infects more than 34 million worldwide. Prevention measures have helped check its spread, while early detection and new antiretroviral drugs can control the disease for decades, meaning it is no longer a death sentence.

But the complexity of the virus has stymied scientists seeking a cure. Antiviral drugs are less than ideal due to factors including cost, side effects and drug resistance.

"You've always got this hanging over your head ... If you could get rid of the virus completely, you could get rid of the concern," said Jay Johnson, a trial participant and Philadelphia volunteer coordinator who was diagnosed with HIV in 1991.

Johnson had a bad reaction to the reinfusion of his altered immune system cells, but reported no side affects afterward. His viral load dropped but then crept back up, prompting him to resume antiretroviral therapy. To control his HIV infection, the 53-year-old takes two pills twice a day, an improvement over his 1990s regimen of five pills three times daily.

"Some of my new cells are being made without the CCR5 receptor and that is promising," he said. "Becoming HIV negative would be wonderful."

Treatment with SB-728-T in the early-stage trial was found to be generally safe, researchers said.

Safety is key, and "they still have to do better with durability," Dr Fauci said. "They've got to try and get to the point where when they stop therapy, the virus doesn't rebound."